More active analgesic combinations are in constant demand because they offer the attractive possibility of relieving pain with reduced dosages thereby diminishing the expected side effects and toxicity that would result from the otherwise required higher dosages.
U.S. Pat. No. 3,393,197, issued to Pachter and Matossian on July 16, 1968, discloses N-substituted-14-hydroxydihydronormorphines, including the N-cyclobutylmethyl derivative, commonly called nalbuphine: ##STR1## Pachter and Matossian and others, such as H. W. Elliott, et al., J. Med. (Basel), 1, 74-89 (1970); H. Blumberg, et al., Pharmacologist, 10, 189 (Fall 1968); P. Roberts, Drugs of the future, 2, 613-5 (1977), disclose the use of nalbuphine as an analgesic for the control of moderate to severe pain.
U.S. Pat. No. 4,237,140, issued to J. R. Dudzinski on Dec. 2, 1980, describes an analgesic mixture of nalbuphine and acetaminophen. U.S. Pat. No. 4,282,215, issued to J. R. Dudzinski and W. K. Schmidt on Aug. 4, 1981, describes an analgesic mixture of nalbuphine and aspirin.
U.S. Pat. Nos. 3,654,349 and 3,647,858 issued to Shen et al. and Hinckley et al., respectively, disclose the synthesis and analgesic utility of (Z)-5-fluoro-2-methyl-1-{[4-(methylsulfinyl)phenyl]methylene}-1H-indene-3- acetic acid, commonly called sulindac: ##STR2## Van Arman et al., Fed. Proc., 31, 577 (1972) disclose the pharmacological properties and metabolism of sulindac. U.S. Pat. No. 4,207,340 issued to J. F. Gardocki describes an analgesic mixture of sunlindac and acetaminophen.